In the related applications filed concurrently herewith and referred to above, applicants disclose several inventions relating to tumor remission and prevention in mammals. One aspect of these inventions is the fractionation, remission and prevention of tumors. These inventions arose, in part, as a result of the assumption that the body has within it an anticancer immune defense mechanism which prevents or controls the formation of tumor cells, and that tumors arise only when this system does not function properly or sufficiently, either due to an imbalance which may be genetic in origin, or the presence of more cancer producing stress than the animal's system can handle.
Based upon the foregoing, applicants proceeded to fractionate mammalian blood. Since the materials sought were unknown in structure, the properties vis a vis their effect on the animal, had to be determined empirically. For example, if a fraction of the animal's blood is injected into a tumor bearing mouse and the tumor does not respond, then the blood may be centrifuged to give a sediment and a supernatant, each of which is again tested on the mice. If again the tumors do not respond, then perhaps the blood fraction is centrifuged at a higher speed and the resultant materials are again tested. If it turns out that the resultant sediment causes a positive anti-tumor response, then it is clear that centrifuging at the higher speed resulted in the separation of a tumor-controlling component. Also considered was the presence of a material in the supernatant which, before being separated from the active sediment, inhibited the tumor activity of the material in the sediment.
Proceeding in the foregoing fashion, the Applicants were able to isolate three blood components or fractions, the presence in balanced proportion of which, both inhibit the formation and cause necrosis of neoplasmic tissue. These components are virtually non-toxic and have no apparent side effects or adverse effect on normal tissue. The toxicity is so minimal that an L.D. 50 has thus far not been obtainable.
As stated in the above-referred to concurrently filed applications, though the chemical structure of these components has not been illucidated, the materials have been identified and named as follows:
1. Tumor Complement Fraction ("TCF")
a peptide chain or derivative thereof that attacks the tumor and causes necrosis of the tumor tissue PA1 a substance that blocks the activity of TCF PA1 a protein or derivative thereof that neutralizes or "de-blocks" BPF TCF, BPF and DPF must be in balance to maintain a tumor free condition. In a normal animal, tumor growth is prevented by the presence of a greater amount of TCF than BPF, there being generally seven units of TCF for each unit of DPF. In a tumor-bearing animal, less TCF is present in the blood. By administering DPF to a tumor-bearing animal, it is theorized that TCF which is bound to the BPF, can be freed again to do its work of killing tumor cells. If TCF is added along with DPF, the necrosis of tumor tissue can be made to proceed at a more rapid rate. Thus, the essence of tumor treatment according to the principles stated in the above-referred to applications, is to administer TCF and/or DPF to thereby provide free TCF capable of necrosizing the tumorous tissue.
2. Blocking Protein Fraction ("BPF")
3. De-Blocking Protein Fraction ("DPF")
As a collorary to the foregoing conclusions, it was concluded that BPF has an inactivating effect on the body's immune defense system and can be used to prevent tissue implant rejection and it has been found that this is the case.
BPF is also useful in assaying the activity of TCF and DPF which, as disclosed in the above-referred to concurrently filed pending applications, are useful in effecting necrosis of tumor tissue.
Accordingly, it is one object of the present invention to provide a method of extracting BPF from mammalian blood without significantly altering or modifying the material from its in vivo condition.
It is a further object of the present invention to provide a mammalian blood component which tends to inactivate the body's immune defense system thereby reducing the tendency of the body to reject tissue implants.
It is a still further object of the present invention to provide a material which can be used to assay the anti-tumor activity of TCF and DPF.